Noradrenergic Dysregulation, Sleep and Cognition in Older Adults With Insomnia

Inclusion criteria

• Age ≥ 55 years;
• Independent in activities of daily living and without clinically significant cognitive impairment as determined by a mini-mental status examination (MMSE) score ≥ 26;
• Due to the effect of reproductive hormones on autonomic regulation, sleep and cognition, women will be postmenopausal;
• time spent in bed not greater than 8.5 hours;
• Sedentary, defined as participation in exercise of moderate intensity for less than 30 minutes per day and less than two times per week on a regular basis.
• average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria

for the insomnia group:

• Meet criteria for chronic insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
• Subjective sleep efficiency less than 85% and/or awakening earlier than desired if before 6 AM for ≥3 nights/week in the previous 4 weeks;
• Subjective WASO (sWASO) ≥ 60 minutes for ≥3 nights/week in previous 4 weeks. sWASO will include time spent awake after sleep onset before final awakening + time spent awake in bed attempting to sleep after the final awakening;
• global PSQI score greater than 5;
• average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria

for the control group:

• No history of chronic or short-term insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
• Subjective sleep efficiency greater than 85%;
• Subjective mean total sleep time of 6.5 hours to 8 hours;
• Habitual bedtime of 9PM-midnight;
• PSQI score ≤ 5. Participants in the control group will be matched with the insomnia group on sex and age (±3 years).

Exclusion criteria

• Sleep disorders other than insomnia (restless legs syndrome, parasomnias, REM behavior disorder, circadian rhythm sleep-wake disorder, sleep apnea by STOP questionnaire and apnea hypopnea index (AHI) ≥ 15 by home sleep apnea test;
• habitual bedtime before 9pm or morning awakening before 5am;
• History of neurological disorders;
• History of psychiatric disorders;
• A Beck depression inventory ((BDI-II) score greater than 19);
• Unstable or serious medical conditions;
• Prediabetes and diabetes (HbA1C ≥ 5.7)
• Current, or use within the past month, of psychoactive, hypnotic, stimulant or analgesic medications (except occasionally);
• Use of medications that interfere with NA system activity including B-blockers, selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective norepinephrine-dopamine reuptake inhibitors (NDRIs);
• Hormone replacement therapy;
• Use of medications that affects pupil diameter and responses to light (i.e. antihistamines, anticholinergics, benzodiazepines, narcotics for pain;
• History of visual abnormalities that may interfere with pupillary responses to light exposure such as significant cataracts, narrow-angle glaucoma or blindness;
• History of heart conditions (i.e. arrhythmia, coronary artery disease, angina, heart failure);
• Shift work or other types of self-imposed irregular sleep schedules;
• BMI > 35 kg/m2;
• History of habitual smoking (6 or more cigarettes/week) or caffeine consumption > 400 mg/day.

17.Use of weight-loss medications